Self-folding cavitands of nanoscale dimensions

New types of resorcinarene-based nanoscale container molecules 2 and 3 are described. They feature reversibly folding unimolecular cavities of nanoscale dimensions and similar to 800 Angstrom(3) internal volume: they are among the largest synthetic unimolecular hosts prepared to date. Two seams of intramolecular hydrogen bonds, provided by 12 secondary amides, control the guest uptake and release. The hydrogen bonds resist the unfolding of the host and increase the energetic barrier to guest exchange. Exchange is slow on the NMR time scale (room temperature), and kinetically stable complexes result. The direct observation of bound species and the stoichiometry of the complexes are reported. A series of adamantyl and cyclohexyl guests 11-19 of various shapes and lengths were prepared and used to estimate the hosts' capacities. Compound 2 exists in an S-shaped conformation and its two cavities act independently; each half of host 2 formed kinetically stable complexes with either two identical or different guest molecules. The C-shaped host 3 accommodates rigid and long guests with association constants (K-a) between 500 +/- 50 M-1 (-Delta G(295) = 3.6 +/- 0.1 kcal mol(-1)) and 270 +/- 100 M-1 (-Delta G(295) = 3.2 +/- 0.2 kcal mol(-1)) for adamantyl derivatives. With the more flexible and/or shorter guests, fast exchange between the free and complexed guest species was observed at room and higher temperatures (in toluene-d(8)). Guest exchange rates of the new hosts are considerably faster than rates seen with typical hemicarceplexes but slower than those of other open-ended cavitands.